We have previously demonstrated the feasibility of using the urine version of the monoclonal antibody BrE-3 for high-dose radioimmunotherapy in patients with breast cancer (CaRes55:5921s, 1995). We have now initiated a Phase I study of a single injection of 90-Y labeled MX-DTPA-humanized-BrE- 3 followed by G-CSF mobilized autologous hematopoietic stem cells support in patients with refractory metastatic breast cancer followed by systemic G-CSF. 111-In-labeled hu-BrE was co-injected for imaging and dosimetry purposes. To date, nine patients have been treated in the first three cohorts. Patients received a dose of 90-Y of 10 mCi/m2 (n=3), 20 mCi/m2 (n=3), or 30 mCi/m2 followed 14 days later by ASCS. No non-hematologic non-infectious toxicities were seen in any of the patients. In one patient (2nd cohort) the neutrophil nadir was below 500 mm3 and resulted in uncomplicated febrile neutropenia. Two patients had platelet nadirs below 20,000 mm3. All the patients recovered multi lineage hematopoiesis. Known metastatic lesions were detected in all patients including: lung, bone, subcutaneous tissue, and liver. Mean half-life of 90-Y was 77.9 hs (74.7-82.2). Radiation absorbed dose estimates for 90-Y in the first two patients, extrapolated from 111-In, were 2.81 and 2.94 cGy/mCi for the whole body. Responses were: 1 partial response, 1 mixed response, 1 minimal response, 1 clinical improvement (no measurable disease). Dose escalation continues until the maximum tolerated dose is reached.